Antibodies that bind to polypeptides expressed on the surface of cancer cells have proven to be effective anti-cancer therapies. Such antibodies act through various mechanisms including, for example, activation of antibody-dependent cell-mediated cytotoxicity (ADCC); induction by the antibody of complement-dependent cytotoxicity (CDC); enhancement of cytokine release; and induction of apoptosis. See, e.g, Cardarelli et al. (2002) Cancer Immunol. Immunother. 51:15-24. For example, HERCEPTIN® and RITUXAN® (both from Genentech Inc., South San Francisco, Calif.) are antibodies that have been used successfully to treat breast cancer and non-Hodgkin's lymphoma, respectively. HERCEPTIN® is a recombinant DNA-derived humanized monoclonal antibody that selectively binds to the extracellular domain of the human epidermal growth factor receptor 2 (HER2) proto-oncogene. HER2 protein overexpression is observed in 25-30% of primary breast cancers. RITUXAN® is a genetically engineered chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes. Both these antibodies are recombinantly produced in CHO cells. HERCEPTIN® appears to act, at least in part, by inhibiting angiogenesis (Izumi et al. (2002) Nature 416:279-280), and RITUXAN® appears to act, at least in part, by inducing apoptosis (Cardarelli et al. (2002) Cancer Immunol. Immunother. 51:15-24).
Immunoconjugates, or “antibody-drug conjugates,” are useful for the local delivery of cytotoxic agents in the treatment of cancer. See, e.g., Syrigos et al. (1999) Anticancer Research 19:605-614; Niculescu-Duvaz et al. (1997) Adv. Drug Deliv. Rev. 26:151-172; U.S. Pat. No. 4,975,278. Immunoconjugates allow for the targeted delivery of a drug moiety to a tumor, whereas systemic administration of unconjugated cytotoxic agents may result in unacceptable levels of toxicity to normal cells as well as the tumor cells sought to be eliminated. See Baldwin et al. (Mar. 15, 1986) Lancet pp. 603-05; Thorpe (1985) “Antibody Carriers Of Cytotoxic Agents In Cancer Therapy: A Review,” in Monoclonal Antibodies '84: Biological and Clinical Applications (A. Pinchera et al., eds.) pp. 475-506. Immunoconjugates that target cell surface polypeptides have been and continue to be developed for the treatment of cancer. For review, see, e.g., Hamann et al. (2005) Expert Opin. Ther. Patents (2005) 15:1087-1103.
It is clear that there is a continuing need for agents that target cell surface polypeptides for diagnostic and/or therapeutic purposes. The invention described herein meets this need and provides other benefits.
All references cited herein, including patent applications and publications, are incorporated by reference in their entirety.